Modeling of In-Utero and Intra-Partum Transmissions to Evaluate the Efficacy of Interventions for the Prevention of Perinatal HIV

Patumrat Sripan (1, 2) , Sophie Le Coeur (3, 1) , Billy Amzal (1) , Lily Ingsrisawang (4) , Patrinee Traisathit (5) , Nicole Ngo-Giang-Huong (1, 5) , Ken Mcintosh (6) , Timothy Cressey (1, 5) , Suraphan Sangsawang , Boonsong Rawangban , Prateep Kanjanavikai , Jean-Marc Treluyer (7, 8, 9) , Gonzague Jourdain (1, 5) , Marc Lallemant (1) , Saik Urien (7, 8, 9)

1 IRD - Institut de Recherche pour le Développement
2 UP11 - Université Paris-Sud - Paris 11
3 INED - Institut national d'études démographiques
4 KU - Kasetsart University [Bangkok, Thailand]
5 CMU - Chiang Mai University
6 HMS - Harvard Medical School [Boston]
7 UPD5 - Université Paris Descartes - Paris 5
8 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
9 CIC 1419 - CIC - Mère Enfant Necker Cochin Paris Centre

BACKGROUND: Antiretroviral treatments decrease HIV mother-to-child transmission through pre/post exposure prophylaxis and reduction of maternal viral load. We modeled in-utero and intra-partum HIV transmissions to investigate the preventive role of various antiretroviral treatments interventions. METHODS: We analysed data from 3,759 women-infant pairs enrolled in 3 randomized clinical trials evaluating (1) zidovudine monotherapy, (2) zidovudine plus perinatal single-dose nevirapine or (3) zidovudine plus lopinavir/ritonavir for the prevention of mother-to-child transmission of HIV in Thailand. All infants were formula-fed. Non-linear mixed effect modeling was used to express the viral load evolution under antiretroviral treatments and the probability of transmission. RESULTS: Median viral load was 4 log10 copies/mL (Interquartile range: 3.36-4.56) before antiretroviral treatments initiation. An Emax model described the viral load time-course during pregnancy. Half of the maximum effect of zidovudine (28% decrease) and lopinavir/ritonavir (72% decrease) were achieved after 98 and 12 days, respectively. Adjusted on viral load at baseline (Odds ratio = 1.50 [95% confidence interval: 1.34, 1.68] per log10 copies/mL increment), antiretroviral treatments duration (OR = 0.80 [0.75, 0.84] per week increment) but not the nature of antiretroviral treatments were associated with in-utero transmission. Adjusted on gestational age at delivery (<37 weeks, OR = 2.37 [1.37, 4.10]), baseline CD4 (Odds ratio = 0.79 [0.72, 0.88] per 100 cells/mm3 increment) and predicted viral load at delivery (OR = 1.47 [1.25, 1.64] per log10 copies/mL increment), single-dose nevirapine considerably reduced intra-partum transmission (OR = 0.32 [0.2, 0.51]). CONCLUSION: These models determined the respective contributions of various antiretroviral strategies on prevention of mother-to-child transmission. This can help predict the efficacy of new antiretroviral treatments and/or prevention of mother-to-child transmission strategies particularly for women with no or late antenatal care who are at high risk of transmitting HIV to their offspring. TRIAL REGISTRATION: This analysis is based on secondary data obtained from three clinical trials. ClinicalTrials.gov. NCT00386230, NCT00398684, NCT00409591.

Mots clés: Vertical; Viral Load; Theoretical; Pregnancy; Models; Female; HIV Infections/prevention & control/transmission; Humans; Infant; Infectious Disease Transmission

Domaines: Maladies infectieuses; Santé publique et épidémiologie; Gynécologie et obstétrique

Patumrat Sripan, Sophie Le Coeur, Billy Amzal, Lily Ingsrisawang, Patrinee Traisathit, et al.. Modeling of In-Utero and Intra-Partum Transmissions to Evaluate the Efficacy of Interventions for the Prevention of Perinatal HIV. PLoS ONE, 2015, 10 (5), pp.e0126647. ⟨10.1371/journal.pone.0126647⟩. ⟨hal-02082679⟩